104. Interleukin (IL)-4 knockout (KO) mice show anxiety-like behaviors that appear dependent on IL-1 receptor antagonist (RA)

Abstract

The anti-inflammatory cytokine IL-4 is a key inducer of IL-1RA production as well as a regulator of spatial memory. Here we examined adverse behaviors in IL-4 KO mice. In the novel object recognition test, IL-4 KO mice, like wild type (WT) mice, preferentially explored a novel object over a familiar object. Total exploration time of both novel and familiar objects was reduced in the IL-4 KO mice compared to WT mice. Assessment of mouse movement using spontaneous locomotor activity (LMA) demonstrated that IL-4 KO mice moved up to 50% less than WT. Similarly, burrowing behavior was reduced by up to 67% in IL-4 KO mice compared to WT mice, as was exploration of the open areas of elevated zero maze (IL-4 KO vs WT mice, 55% reduced). Examination of immune-associated gene transcripts in the brain confirmed that IL-4 KO mice lack IL-4 compared to WT, and brain expression of CD11b, F4/80, IL-1α, IL-1β, IL-1R1, IL-1R2, IL-1RA, and IL-6 were similar in IL-4 KO and WT mice. Finally, induction of foreign body-associated inflammation in the brains of IL-4 KO mice normalized LMA between IL-4 KO mice and similarly treated WT mice, in that intracerebroventricular (icv) cannulation caused IL-1RA brain message to increase 20-fold. We deduced that lack of IL-4-dependent production of IL-1RA may be critical to the adverse behaviors seen in IL-4 KO mice.